Multiple sclerosis or MS is a disease that affects the brain and spinal cord resulting in loss of muscle control, vision, balance, sensation (such as numbness) or thinking ability.
In MS, parts of the brain and spinal cord, which together form the central nervous system or CNS are recognized as being foreign and are attacked by one's own immune system. At the cellular level, the CNS is made up by neurons, the “thinking cells” of the nervous system, and glial cells, which perform a wide variety of vital functions. The cell bodies of the neurons are connected to one-another by axons, which function like wires tying neuronal networks together. There are billions of axons in the CNS, which, like copper wires, need to be insulated to prevent loss of signaling, to boost the speed of signaling and to prevent signal interference. The insulating material of the CNS, called myelin, is a specialized organelle of glial cells, which wrap the myelin around the axons. In MS, elements of myelin are recognized as foreign, and are attacked by the individual's own immune system. As a result of these immune attacks the myelin is destroyed, and often, the associated axons are also damaged leading to death. This is an iterative process broken up by periods of remyelination. However, while myelin can reform, eventually the pool of cells that can make myelin is depleted, resulting in areas of chronic CNS demyelination that eventually form scars, also known as plaques, and whose formation is known as sclerosis. When this process of sclerosis is iterative, the resulting form of MS is called relapsing/remitting MS. There is also another rarer form of MS, called primary progressive MS, where no remission occurs. In either case, without the myelin, electrical signals transmitted throughout the brain and spinal cord are disrupted or halted. The affected areas of the brain then become unable to properly send and to receive messages. It is this breakdown of communication that causes the symptoms of MS.
There are a variety of medications available that can reduce the frequency and severity of MS symptoms in some people with MS. Symptoms may be divided into three categories: primary, secondary, and tertiary. Primary symptoms are a direct result of the demyelination process. This impairs the transmission of electrical signals to muscles (to allow them to move appropriately) and the organs of the body (allowing them to perform normal functions.) The symptoms include: weakness, tremors, tingling, numbness, loss of balance, vision impairment, paralysis, and bladder and bowel problems.
Secondary symptoms result from primary symptoms. For example, paralysis (a primary symptom) can lead to bedsores (pressure sores) and bladder or urinary incontinence problems can cause frequent, recurring urinary tract infections. These symptoms can be treated, but the ideal goal is to avail them by treating the primary symptoms.
Tertiary symptoms are the social, psychological, and vocational complications associated with the primary and secondary symptoms. Depression, for example, is a common problem among people with MS.
The course of multiple sclerosis is highly variable. In particular, the earliest stages of the disease can be somewhat unpredictable. Because of this uncertainty, doctors often tell their patients that they “probably” or “possibly” have MS. Diagnosis is based on the combination of clinical presentations, findings on magnetic resonance imaging (“MM”) and other tests, and patterns of recurrence. At present there is no way to predict how each person's disease will progress. It often takes an extended period of time before a definitive diagnosis of MS can be made. There are three main courses that MS takes:
Relapsing-remitting MS (“RRMS”): characterized by unpredictable acute attacks, called “exacerbations,” with worsening of symptoms followed by full, partial or no recovery of some function. These attacks appear to evolve over several days to weeks. Recovery from an attack takes weeks sometimes months. The disease does not worsen in the periods between the attacks. This pattern usually occurs early in the course of MS in most people.
Primary-progressive MS: characterized by a steady progression of disability, without any obvious relapses and remissions. This form of disease occurs in just 15% of all people with MS, but is more common in people who develop the disease after the age of 40.
Secondary-progressive MS: initially begins with a relapsing-remitting course, but later evolves into progressive disease. The progressive part of the disease may begin shortly after the onset of MS, or it may occur years or decades later.
A true exacerbation of MS is caused by an area of inflammation (i.e. swelling) in the nerves of the brain and spinal cord system followed by something called demyelination, which is the destruction of myelin. The myelin is the fatty sheath that surrounds and protects the nerve fibers. An exacerbation of MS may be mild and not cause a noticeable impairment in functioning or may significantly interfere with a person's daily life. Untreated, exacerbations can last from several days to several weeks, although they may extend into months.
Current therapy intended to slow MS progression has many difficulties. A number of drugs have been shown to slow the progression of MS in some people. These drugs work by suppressing, or altering, the activity of the body's immune system. Thus, these therapies are based on the theory that MS is, at least in part, a result of an abnormal response of the body's immune system that causes it to attack the myelin surrounding nerves. While these disease modifying treatments have altered the natural history of RRMS in many patients, they are non-curative and have significant adverse effects including the sequelae of systemic immunosuppression, as well as fever, body pains, malaise, arthralgia, myalgias, flu-like symptoms, liver function test (LFT) elevations, activation of latent viruses, including John Cunningham (JC) virus, which leads to the oft-lethal Progressive Multifocal Leukoencephalopathy (PML), and more. As a result, the treatments are poorly tolerated by a significant number of patients when given at therapeutic doses and breakthrough disease activity is virtually a given. For the 30% of patients who are either non-responsive, or who have only partial drug-responses (˜19%), or for those that do not tolerate therapeutic dosages of otherwise effective drug, there are very limited alternatives. Examples include Avonex® (interferon beta-1a; Avonex is a registered trademark of Biogen Idec MA Inc.), Betaseron® (interferon beta-1b; Betaseron is a registered trademark of Bayer Pharma), Copaxone® (Glatiramer acetate; Copaxone is a registered trademark of Teva Pharmaceutical Industries), Novantrone® (mitoxantrone; Novantrone is a registered trademark of Immunex Corporation), Rebif® (interferon beta-1a; Rebif is a registered trademark of Ares Trading), Tysabri® (natalizumab; Tysabri is a registered trademark of Elan Pharmaceuticals), Tecfidera® (BG12; Tecfidera is a registered trademark of Biogen Idec), Laquinimod™ (Laquinimod is a trademark of Teva Pharmaceuticals) and Aubagio® (Teriflunomide; Aubagio is a registered trademark of Sanofi).
Other undesirable characteristics of these drug therapies include unpleasantness, pain and discomfort associated with injections, leukopenia, opportunistic infections, nausea, vomiting, diarrhea, alopecia, flushing, high cost and drug instability. Accordingly, there is still a need in the art for a safe and effective method for slowing the progression, treatment and alleviating symptoms of MS.
The deterioration of these physical and cognitive functions can also be the result of both neuroinflammation and gray matter loss that is part of the MS neuropathologic process. While immunomodulation and disease modification is partially achieved with the current first-line drugs, they do not provide overall neuroprotection which would be considered the holy grail of therapy.